It is widely believed that pain affects men and women differentially; females demonstrate significantly higher[unreadable] behavioral responses to chronic and inflammatory pain than males. Sex differences in the experiences of[unreadable] pain reside in part in intrinsic biological differences; i.e., changes in pain responses associated with[unreadable] physiological fluctuations of gonadal hormones are indicative of a significant contribution of estrogen and[unreadable] progesterone to the regulation of pain responses. We have recently shown that in female rats estrogen[unreadable] produces a persistent analgesic effect on injury (inflammation)-induced pain. Our long-term goal is to[unreadable] determine whether fluctuations during different stages of the female reproductive cycle in inflammatory and[unreadable] persistent pain perception are due to fluctuations in estrogen. The objective of this proposal is to determine if[unreadable] estrogen's analgesic effects on inflammatory/chronic pain are mediated through activation of inflammatory[unreadable] mechanisms. Specifically, we hypothesize that estrogen's antihypera'nalgesic effects on injury[unreadable] (inflammation)-induced pain are mediated through up-regulation of corticosterone release which in turn[unreadable] down-regulates COX-2 protein activity and, thus, prostaglandin-biosynthesis. Studies addressing behavioral[unreadable] responses to pain in females and the role of estrogen in persistent/inflammatory pain are limited.[unreadable] Furthermore, although several publications have studied the effects of estrogen on COX-2 in ovarian tissue,[unreadable] the role of estrogen in the regulation of prostaglandin release in the peripheral and central nervous system[unreadable] has been little studied.